Nanotech Remains a Robust Research Focus

Andrew D. Smith

Published: Friday, Jul 07, 2017

Ennio Tasciotti, PhD

Despite several high-profile setbacks in recent years, efforts to transform cancer care by using nanotechnology to deliver medications directly into patients’ tumors are moving forward, with the FDA’s ongoing review of a novel formulation generating fresh excitement in the field.

CPX-351 (Vyxeos), the first nanotechology drug to combine 2 medications in the same delivery vehicle, is being evaluated under the FDA’s priority review program after producing positive results in a phase III trial against secondary acute myeloid leukemia (AML).1 The drug, which the FDA also has designated a breakthrough therapy, demonstrated a 31% reduction in the risk of death compared with standard chemotherapy in older patients (ages 60-75) with high-risk AML.

Overall, the FDA has approved 6 anticancer therapies that nanotechnology since the first such drugs were cleared for the US market in the 1990s (Table).2 At least 4 other nanotherapeutics are approved in other countries, and more than 2 dozen novel therapies are under study in clinical trials.2

Experts say the fundamental theory that underlies the use of nanotechnology in drug delivery remains compelling and that a greater understanding of tumor biology will improve the prospects for its use in oncology in the future.

“Progress in nanotechnology has gone faster so far than it did with either biologic treatments or immunotherapies. We have learned so much about making nanoparticles, and we are now discovering how they really work in the body and how they interact with cells and tissues,” said Ennio Tasciotti, PhD, co-chair of the Department of Nanomedicine at The Methodist Hospital Research Institute in Houston, in an interview with OncologyLive®. “This line of attack will greatly improve cancer care at some point. It’s just a matter of time.”

The term “nanotechnology” applies to any designed and manufactured object that measures 1 to 100 nm.3 The nanoparticles currently used to deliver cancer medications generally measure 30 to 100 nm. That may sound too small for drug delivery when you consider that a sheet of paper is about 100,000 nm thick4, but there is plenty of space for medicinal cargo. A 100-nm particle dwarfs a chemotherapy molecule to the degree that the Goodyear Blimp dwarfs a soccer ball (Figure).5

Chemotherapy molecules, which are the payload in most therapeutic nanoparticles to undergo latestage trials so far, are so small that they leak out of every blood vessel and poison the entire body. Nanoparticle delivery vehicles, on the other hand, are intentionally designed so that they should be too large to escape from healthy blood vessels, yet small enough to escape many of the hastily built (and therefore somewhat leaky) blood vessels that feed rapidly growing tumors.6

Size was the main advantage of first-generation nanoparticles, which were simple lipid vesicles coated with polyethylene glycol (PEG) to prevent an immune response. Subsequent designs have used particular shapes and ligand coatings to better target tumors, as well as timed chemotherapy release to increase exposure times and encourage the accumulation of medication on tumor tissue. The goal was simple: getting far more medication to tumor cells while virtually eliminating contact between chemotherapy and healthy tissue.7

Table. FDA-Approved Oncology Nanotherapeutics

Disappointing Findings

Intuitively, this approach seems like a surefire strategy. However, clinical trial results have often not lived up to expectations. Many nanoparticle formulations that have undergone late-stage cancer trials have demonstrated no therapeutic advantage over standard therapies; several high-profile developments illustrate this trend.

NK105, a paclitaxel-infused nanoparticle, failed to increase overall survival (OS) in a phase III trial that compared the novel drug with standard paclitaxel in patients with metastatic or recurring breast cancer, Nippon Kayaku, the Japanese company developing the drug, reported in July 2016.8 The nanoparticles used in the experimental formulation were designed both to deliver the medication directly to tumors and to control the timing of its release so as to increase the contact period between paclitaxel and tumor from 30 minutes to 10 hours.